Vascular lesions, comprising enlarged or ectatic blood vessels, pigmented lesions, and tattoos have been successfully treated with lasers for many years. In the process called selective photothermolysis, the targeted structure, the lesion tissue or tattoo pigment particles, and the surrounding tissue are collectively irradiated with laser light. The wavelength or color of this laser light, however, is chosen so that its energy is preferentially absorbed by the target. Localized heating of the target resulting from the preferential absorption leads to its destruction.
Most commonly in the context of vascular lesions, such as portwine stains for example, hemoglobin of red blood cells within the ectatic blood vessels serves as the laser light absorber, i.e., the chromophore. These cells absorb the energy of the laser light and transfer this energy to the surrounding vessel as heat. If this occurs quickly and with enough energy, the vessel reaches a temperature to denature the constituents within the boundary of the vessel. The fluence, Joules per square centimeter, to reach the denaturation of a vessel and the contents is calculated to be that necessary to raise the temperature of the targeted volume within the vessel to about 70xc2x0 C. before a significant portion of the absorbed laser energy can diffuse out of the vessel. The fluence must, however, be limited so that the tissue surrounding the vessel is not also denatured.
As suggested, simply selecting the necessary fluence is not enough. The intensity and pulse duration of the laser light must also be optimized for selectivity by both minimizing diffusion into the surrounding tissue during the pulse while avoiding localized vaporization. Boiling and vaporization lead to mechanical, rather than chemical, damagexe2x80x94which can increase injury and hemorrhage in the tissues that surround the lesion. This constraint suggests that for the fluence necessary to denature the contents of the vessel, the pulse duration should be long and at a low intensity to avoid vaporization. It must also not be too long because of thermal diffusion, however. Energy from the laser light pulse must be deposited before heat dissipates into the tissue surrounding the vessel. The situation becomes more complex if the chromophore is the blood cell hemoglobin within the lesion blood vessels, since the vessels are an order of magnitude larger than the blood cells. Radiation must be added at low intensities so as to not vaporize the small cells, yet long enough to heat the blood vessels by thermal diffusion to the point of denaturation and then terminated before tissue surrounding the blood vessels is damaged.
Conventionally, flashlamp-excited dye lasers have been used as the laser light source. These lasers have the high spectral brightness required for selective photothermolysis and can be tuned to colors at which preferential absorption occurs. For example, wavelengths in the range of 577 to 585 nanometers (nm) match the alpha absorption band of hemoglobin and thus are absorbed well by the red blood cells in the blood vessels. The absorption of melanin, the principal pigment in the skin, is poor in this range, yielding the necessary selectivity.
Flashlamp-excited dye lasers, however, present problems in the pulse length obtainable by this type of laser. Theory dictates that the length of the light pulse should be on the order of the thermal relaxation time of the ectatic vessels or other dermal target. Ectatic vessels of greater than 30 microns in diameter are characteristic of cutaneous vascular lesions. These large vessels have relaxation times of 0.5 milliseconds (msec) and longer and thus require pulse durations of this length. Commercially available flashlamp-excited dye lasers generally have maximum pulse lengths that are shorter than 0.5 msec. Brute force excitation of the dye gain medium can result in pulses as long as 1.5 milliseconds. As a result, selective photothermolysis treatment of ectatic vessels larger than 30 microns currently relies on higher than optimum irradiance to compensate for the pulse duration limitations. This leads to temporary discoloration of the skin, viz., purpura.
With shorter than desirable pulse durations, purpura, which is a bluish lesion that appears as black and blue spots, forms at the treated site. It is not medically harmful nor is it permanent, and lasts but a couple of weeks. Patients prefer not to have this cosmetically undesirable side effect. It is commonly believed that pulses longer than 5 msec will reduce the formation of purpura.
Dierickx, et al., xe2x80x9cThermal Relaxation of Port Wine Stain Vessels Probed In-Vivo: The Need for 1-10 Millisecond Laser Pulse Treatments,xe2x80x9d J. of Investigative Dermatology, 105, 709-714, (1995) report the data and histologic assessment of the vessel injury strongly suggest that pulse durations for ideal laser treatment are in the 1-10 millisecond region and depend on vessel diameter. No dermatologic laser presently used for port wine stain treatment operates in this pulse width domain. Commercial medical dye lasers with pulse durations of 1.5 msec are now available but these lasers do not show the needed improvement in the treatment of ectatic vessels. Moreover, the combination of two dye lasers was suggested to generate 4.5 msec pulses according to U.S. Pat. No. 5,746,735 and the output used in leg vein treatment. The results showed marginal improvement over pulses 1.5 msec long. See Alora M. B., et al., xe2x80x9cComparison of the 595 nm Long Pulse (1.5 ms) and 595 nm Ultra Long Pulse (4 ms) Laser in Treatment of Leg Veins,xe2x80x9d American Society Laser Medicine 18th Annual Meeting Supplement 10, No. 158, (1998). It is therefore desirable to get to 10 msec and longer.
In dye lasers, it has been observed that the premature cessation of the lasing is caused primarily by the degradation of the dye solution. Improved dye solution_ formulations can yield some increases in pulse duration. Dye degradation, however, cannot be totally eliminated and other steps must be taken if pulse durations of 5 msec and longer and having the fluences for medical procedures are to be achieved.
One attempt at lengthening the pulse du ration utilizes a flashlamp-excited dye lasers that has a dye cell that permits rapid dye solution interchange during the laser excitation pulse. Specifically, the dye in the dye cell is replaced while the flashlamps are fired so that exhausted and degraded dye medium is removed from the resonant cavity and replaced with fresh dye medium during the excitation pulse, thereby facilitating the lengthening of the laser pulse. The approach is similar to that used to generate laser emission in cw dye lasers, albeit at the much higher energies required for these medical applications.
The batch replacement of dye solution and subsequent processing of the dye solution to lengthen the pulse duration in dye lasers has met with some success. Nonetheless, still longer pulses are required in some cases than currently appear practical using this technique.
The problem that appears to limit the practicality of this technique concerns the fact that it suboptimally uses the flashlamps. The low peak current may not be high enough to excite the dye gain medium well above threshold and the current below threshold is wasted making the long continuous pulse dye laser very inefficient. A preferred mode of operation for the dye laser to generate long, effective laser pulses is to use a sequence of short on and off flashlamp pulses. To generate long laser pulses without exceeding the explosion point of the flashlamp, the current through the lamp is limited to run safely without damaging the lamp. The short current pulses have peak currents that are well above the lasing threshold. The pulse duration of the individual pulse is short enough so as to be well below the explosion point of the flashlamp. If the time when the flashlamp is on and when it is off is shorter than the thermal relaxation time of the target to be heated, the heating effect is nearly the same as if the flashlamp was continuously on.
The above technique allows heating of a target by a sequence of on/off or pulse periodic pulses to be nearly the same as if the flashlamp is continually on, but does not compensate for loss of efficiency caused by degradation of the dye gain medium. But if the dye gain medium that is degraded by the excitation pulse could be extracted from the active gain volume before the next excitation pulse arrives, the dye gain medium will be fresh and not contain degraded dye solution that lessens the gain of the laser. Efficiency of the laser is therefore doubly enhanced by periodic pulsing, first by having flashlamp excitation pulse that is well above threshold, and secondly by removal of degraded gain dye solution when the flashlamp is not excited.
Consequently, the present invention is directed to a technique for generating long effective pulses. The degraded dye is removed during the long effective pulse. However, pulse periodic heating technique is used to preserve the flashlamps. The long effective pulse is optimal for therapeutic treatment, such as selective photothermolysis. This long effective pulse is comprised of much shorter subpulses across the duration of the effective pulse. The flashlamps are fired for only these short, but relatively intense pulses. In this way, the flashlamp useful life is preserved, since the flashlamp will be driven for only a few milliseconds to as short at microseconds. Moreover, overall pumping efficiency is improved since a greater percentage of the generated light is above the lasing threshold for the dye.
In some ways, this operation of a flashlamp-excited dye laser is similar to that used previously in isotope separation. Very high power laser beams were generated using very intense, but short, flashlamp pulses, in which the dye media was replaced.
The difference, relative to the present invention,, is that a pre-defined number of subpulses are created to yield a carefully controlled effective pulse duration that will be therapeutically efficacious. In contrast, the dye lasers used for isotope separation, operated essentially continuously with flashlamps pulsing at a rate of 100 to 1000 pulses per second. Moreover, in the present invention, the heating effect of the subpulse is cumulative on the target, and the total fluence of the effective laser pulse can be carefully controlled to maximize damage to the targeted structure, while minimizing collateral damage. In contrast, in isotope separation, each pulse of the train of pulses acted on new target material and the desired result for the isotope separation process will be degraded if the target material was irradiated more than once.
The pulse periodic operation is achieved by repeatedly triggering the flashlamp(s) while a dye solution is being circulated through the resonant cavity of the laser, typically a dye cell. If the flow velocity of dye solution is great enough, such that the new solution enters the cavity, and the next flashlamp subpulse excites the new fresh dye gain medium, ultra-long-effective pulses with high fluences are possible. Specifically, longer effective pulse duration of up to 50 msec, and longer, can be achieved with energies of up to 50-100 Joules, and greater. These high energies enable treatment with reasonable spot sizes, which makes the invention relevant to medical therapy.
According to one aspect, the invention features a flashlamp-excited dye laser generating light pulses at a color and pulse duration required for selective photothermolysis. This laser preferably comprises a cell containing a laser gain media located in a resonant cavity. Dye solutions are typical examples of such gain media. At least one flashlamp is provided to excite the gain media in the cavity, typically contained in the cell. A circulator is used to circulate the gain media through the cavity. Finally, a controller coordinates operation by triggering the flashlamp to excite the laser gain media, while the circulator is circulating the gain media through the cell. Laser light subpulses are generated with a duration of a few hundred microseconds with a low energy content so as not to create unwanted side effects such as purpura. Though each subpulse has low energy, the thermal effect of the subpulses are cumulative, and the heating effect of the long effective laser pulse is about the same as if the effective laser pulse was on continuously.
For some applications, the effective duration of the output laser light pulse containing the subpulses is preferably at least five milliseconds. Generally, the cumulative energy of the subpulses is about twenty Joules, but can be as large as 50 Joules, which may be necessary for large targets.
In specific embodiments, the circulator replaces gain media in the dye cell with new gain media between the generation of subpulses so that enough new gain media is within the cell to enable the generation of the subsequent subpulse. This operation ensures that the laser output will not be quenched by accumulation of exhausted dye solutions.
Different configurations for the gain media flow through the dye cell can be implemented. In one embodiment, the flow is transverse to the laser axis; in another, the flow is longitudinal, or parallel, to the axis. Preferably, if the longitudinal configurations are implemented, a plurality of media input ports are provided along the cell. A plurality of media output ports are also useful to allow flow out of the cell. The dye cell segments between the adjacent inlet and outlet ports is ideally short so that the residence time of the flowing gain media through the dye cell segment is less than the period between subpulses.
In the transverse flow embodiment, the gain media flows between two parallel or nearly parallel transparent cell walls, which allows the excitation light to enter the dye cell. The transparent cell walls are long in the direction of the flashlamps and laser resonator axis and shorter in the direction of the flow. The gain media flows perpendicular to the long axis of the dye cell and is contained within allow excitation light from the flashlamp to enter the dye cell and within another set of allow the laser light to reflect between mirrors that comprise the laser resonator.
According to another aspect, the invention can also be characterized in the context of a method of operation for a flashlamp-excited dye laser. Such a method comprises exciting the dye solution in the resonant cavity with a flashlamp and then generating a laser light output subpulse from the resonant cavity with the excited dye solution. The excitation at least partially exhausts the dye solution. To counteract this effect, some of the at least partially exhausted dye solution is replaced in the resonant cavity with new dye solution before the generation of the next subpulse, within the duration of the longer effective pulse. The number and cumulative fluence of the subpulses is defined such that the effective pulse duration is appropriate to treat the targeted tissue, while minimizing the detrimental impact on the matrix surrounding the targeted structures.